Introduction: Neuropathic pain after spinal cord injury is one of the most difficult clinical problems after losing mobility, and pharmacological or neuromodulation therapy showed limited efficacy. Because of the complexity of individual spinal injuries and the lack of knowledge in mechanisms underlying NP after SCI, major obstacles still exist for improving the efficacy of treatment. In this study, we investigated pain modulation by a recombinant adeno-associated virus (rAAV) encoding small-hairpin RNA against GCH1 (rAAV-shGCH1) in a spinal cord injury model induced by a spinothalamic tract (STT) lesion.

Methods: We used adult male Sprague Dawley rats and micro-electric lesioning was used to damage the left STT in rats (n = 68), and rAAV-shGCH1 (n = 16) or rAAV control (n = 9) was injected into the dorsal horn of the rats at the same time. For sham group, only STT lesioning was conducted without any treatment. On postoperative days 3, 7, and 14, we evaluated neuropathic pain using a behavioral test and glial cell activation by immunohistochemical staining.

Results: A pain modulation effect of shGCH1 was observed from postoperative days 3 to 14. The mechanical withdrawal threshold was 13.0 ± 0.95 in the shGCH1 group, 4.3 ± 1.37 in the control group, and 3.49 ±0.85 in sham group on postoperative day 3 (p < 0.0001) and continued to postoperative day 14 (shGCH1 vs. control: 11.4 ± 1.1 vs. 2.05 ± 0.60, p < 0.001 and shGCH1 vs. sham: 11.4 ± 1.1 vs. 1.43 ± 0.54, p < 0.001). Immunohistochemical staining of the spinal cord dorsal horn showed deactivation of microglia in the shGCH1 group. However, there was no difference in astrocyte activation between groups.

Conclusion: We confirmed that neuropathic pain after spinal cord injury can be modulated bilaterally by deactivating microglial activation after a unilateral injection of rAAV-shGCH1 into the dorsal horn of a STT lesion spinal cord pain model. This study would be another step to the treatment of neuropathic pain.